Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions.

中文翻译：

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棕榈酰化刺猬肽的蛋白水解加工指定了果蝇翅膀的 3-4 间脉区域

发育过程中的细胞命运决定通常需要形态原从生产细胞到远处响应细胞的运输。Hedgehog (Hh) morphogens 对这一概念提出了挑战，因为所有 Hhs 都是作为末端脂化分子合成的，在生产细胞的表面形成不溶性簇。虽然一些提议的 Hh 传输模式直接与这些不寻常的特性有关，但 Hh 从产生细胞到远程响应细胞上的受体的关键步骤仍未解决。使用黑腹果蝇的翅膀发育作为模型，我们表明 Hh 中继和 3-4 间静脉区域的直接模式严格依赖于脂化 N 末端膜锚的蛋白水解去除。N 端 Hh 加工位点的定点修饰选择性地消除了整个 3-4 间脉区域，和额外的有针对性的去除 N-棕榈酸酯恢复了它的形成。因此，棕榈酰化膜锚会限制形态发生素的传播，直到位点特定处理将膜结合的 Hh 转换为具有特定图案功能的生物活性形式。